The Inter-Dependency of Local Myocardial Metabolism and Epicardial Electrical Activity during Acute Ischemia and Reperfusion

Abstract

Metabolic changes caused by the lack of adequate coronary flow lead to short and long term disturbances in local activation sequences. Our goal has been to study short term disturbances using parallel fluorescence imaging of epicardial NADH (fNADH) and transmembrane potential (TMP). METHODS: Experiments were conducted using Langendorff-perfused rat hearts while controlling the rate of flow to the left anterior descending coronary artery (LAD). Acute regional ischemia was induced by stopping flow to the LAD, followed by a period of low-flow reperfusion with subsequent full-flow reperfusion. Changes in local epicardial conduction velocities, as well as the incidence and dispersion of epicardial breakthroughs, were analyzed with the corresponding local changes of fNADH. With this approach, conduction velocities and reentrant activity could be correlated with changes in fNADH. RESULTS: Regional ischemia led to a reduction in Purkinje fiber activity within the ischemic zone. Approx 4 minutes after the initiation of ischemia, conduction velocities increased within regions with elevated fNADH. Afterward, conduction velocities in the ischemic zone declined and were lowest in the center, eventually falling to values below 20 cm/sec. Reductions in conduction velocity lagged behind elevations of fNADH, both in time and space. During regional ischemia, occasional breakthroughs occurred, most of them along the boundary between ischemic and normoxic tissue. During low-flow reperfusion, the number of breakthroughs within the ischemic zone increased dramatically as well as the incidence of ventricular fibrillation (compared to ischemia and normal flow conditions). CONCLUSIONS: The inter-dependence of local activation patterns and local myocardial metabolism makes parallel imaging of fNADH and TMP an essential tool for understanding the mechanisms of arrhythmias caused by ischemia and reperfusion.